The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis

Sara Elena Rebuzzi; Alessio Signori; Marco Stellato; Daniele Santini; Marco Maruzzo; Ugo De Giorgi; Paolo Pedrazzoli; Luca Galli; Paolo Andrea Zucali; Emanuela Fantinel; Claudia Carella; Giuseppe Procopio; Michele Milella; Francesco Boccardo; Lucia Fratino; Roberto Sabbatini; Riccardo Ricotta; Stefano Panni; Francesco Massari; Mariella Sorarù; Matteo Santoni; Alessio Cortellini; Veronica Prati; Hector Josè Soto Parra; Francesco Atzori; Marilena Di Napoli; Orazio Caffo; Marco Messina; Franco Morelli; Giuseppe Prati; Franco Nolè; Francesca Vignani; Alessia Cavo; Giandomenico Roviello; Miguel Angel Llaja Obispo; Camillo Porta; Sebastiano Buti; Giuseppe Fornarini; Giuseppe Luigi Banna

doi:10.3389/fonc.2022.955501

The prognostic value of baseline and early variations of peripheral blood inflammatory ratios and their cellular components in patients with metastatic renal cell carcinoma treated with nivolumab: The Δ-Meet-URO analysis

Front Oncol. 2022 Sep 23:12:955501. doi: 10.3389/fonc.2022.955501. eCollection 2022.

Authors

Sara Elena Rebuzzi^{1

2}, Alessio Signori³, Marco Stellato⁴, Daniele Santini⁵, Marco Maruzzo⁶, Ugo De Giorgi⁷, Paolo Pedrazzoli^{8

9}, Luca Galli¹⁰, Paolo Andrea Zucali^{11

12}, Emanuela Fantinel¹³, Claudia Carella¹⁴, Giuseppe Procopio⁴, Michele Milella¹³, Francesco Boccardo¹⁵, Lucia Fratino¹⁶, Roberto Sabbatini¹⁷, Riccardo Ricotta¹⁸, Stefano Panni¹⁹, Francesco Massari^{20

21}, Mariella Sorarù²², Matteo Santoni²³, Alessio Cortellini^{24

25}, Veronica Prati²⁶, Hector Josè Soto Parra²⁷, Francesco Atzori²⁸, Marilena Di Napoli²⁹, Orazio Caffo³⁰, Marco Messina³¹, Franco Morelli³², Giuseppe Prati³³, Franco Nolè³⁴, Francesca Vignani³⁵, Alessia Cavo³⁶, Giandomenico Roviello³⁷, Miguel Angel Llaja Obispo³⁸, Camillo Porta^{39

40}, Sebastiano Buti^{41

42}, Giuseppe Fornarini³⁸, Giuseppe Luigi Banna⁴³

Affiliations

¹ Medical Oncology Unit, Ospedale San Paolo, Savona, Italy.
² Department of Internal Medicine and Medical Specialties (Di.M.I.), University of Genova, Genova, Italy.
³ Department of Health Sciences, Section of Biostatistics, University of Genova, Genova, Italy.
⁴ SS Oncologia Medica Genitourinaria, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
⁵ Department of Medical Oncology, Università Campus Bio-Medico of Roma, Rome, Italy.
⁶ Oncology Unit 1, Istituto Oncologico Veneto IOV - IRCCS, Padova, Italy.
⁷ Department of Medical Oncology, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
⁸ Department of Internal Medicine and Medical Therapy, University of Pavia, Pavia, Italy.
⁹ Medical Oncology Unit, IRCCS Policlinico San Matteo, Pavia, Italy.
¹⁰ Medical Oncology Unit 2, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
¹¹ Department of Biomedical Sciences, Humanitas University, Milano, Italy.
¹² Department of Oncology, IRCCS, Humanitas Clinical and Research Center, Milano, Italy.
¹³ Department of Oncology, Azienda Ospedaliera Universitaria Integrata di Verona, University of Verona, Verona, Italy.
¹⁴ Division of Medical Oncology, IRCCS Istituto Tumori "Giovanni Paolo II", Bari, Italy.
¹⁵ Academic Unit of Medical Oncology, IRCCS Ospedale Policlinico San Martino of Genova, Genova, Italy.
¹⁶ Department of Medical Oncology, Centro di Riferimento Oncologico di Aviano CRO-IRCCS, Aviano, Italy.
¹⁷ Medical Oncology Unit, Department of Oncology and Hemathology, University Hospital of Modena, Modena, Italy.
¹⁸ Oncology Unit, IRCCS MultiMedica, Milan, Italy.
¹⁹ Medical Oncology Unit, ASSTl- Istituti Ospitalieri Cremona Hospital, Cremona, Italy.
²⁰ Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
²¹ Department of Experimental, Diagnostic and Specialty Medicine, S. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
²² U. O. Oncologia, Ospedale di Camposampiero, Padova, Italy.
²³ Oncology Unit, Macerata Hospital, Macerata, Italy.
²⁴ Department of Surgery and Cancer, Imperial College London, Faculty of Medicine, Hammersmith Hospital, London, United Kingdom.
²⁵ Department of Biotechnology and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
²⁶ Department of Medical Oncology, Ospedale Michele e Pietro Ferrero, Verduno, Italy.
²⁷ Department of Oncology, Medical Oncology, University Hospital Policlinico-San Marco, Catania, Italy.
²⁸ Medical Oncology Department, University Hospital, University of Cagliari, Cagliari, Italy.
²⁹ Department of Urology and Gynecology, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy.
³⁰ Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
³¹ UOC Oncologia Medica, Istituto Fondazione G. Giglio, Cefalù, Italy.
³² Oncology Department, Gemelli Molise, Campobasso, Italy.
³³ Department of Oncology and Advanced Technologies AUSL - IRCCS, Reggio Emilia, Italy.
³⁴ Medical Oncology Division of Urogenital and Head and Neck Tumors, IEO, European Institute of Oncology IRCCS, Milano, Italy.
³⁵ Division of Medical Oncology, Ordine Mauriziano Hospital, Torino, Italy.
³⁶ Oncology Unit, Villa Scassi Hospital, Genova, Italy.
³⁷ Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Firenze, Firenze, Italy.
³⁸ Medical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
³⁹ Interdisciplinary Department of Medicine, University of Bari "A. Moro", Bari, Italy.
⁴⁰ Division of Medical Oncology, A.O.U. Consorziale Policlinico di Bari, Bari, Italy.
⁴¹ Medical Oncology Unit, University Hospital of Parma, Parma, Italy.
⁴² Department of Medicine and Surgery, University of Parma, Parma, Italy.
⁴³ Department of Oncology, Portsmouth Hospitals University NHS Trust, Portsmouth, United Kingdom.

Abstract

Background: Treatment choice for metastatic renal cell carcinoma (mRCC) patients is still based on baseline clinical and laboratory factors.

Methods: By a pre-specified analysis of the Meet-URO 15 multicentric retrospective study enrolling 571 pretreated mRCC patients receiving nivolumab, baseline and early dynamic variations (Δ) of neutrophil, lymphocyte, and platelet absolute cell counts (ACC) and their inflammatory ratios (IR) were evaluated alongside their association with the best disease response and overall (OS) and progression-free survival (PFS). Multivariable analyses on OS and PFS between baseline and Δ ACC and IR values were investigated with receiving operating curves-based cut-offs.

Results: The analysis included 422 mRCC patients. Neutrophil-to-lymphocyte ratio (NLR) increased over time due to consistent neutrophil increase (p < 0.001). Higher baseline platelets (p = 0.044) and lower lymphocytes (p = 0.018), increasing neutrophil Δ (p for time-group interaction <0.001), higher baseline IR values (NLR: p = 0.012, SII: p = 0.003, PLR: p = 0.003), increasing NLR and systemic immune-inflammatory index (SII) (i.e., NLR x platelets) Δ (p for interaction time-group = 0.0053 and 0.0435, respectively) were associated with disease progression. OS and PFS were significantly shorter in patients with baseline lower lymphocytes (p < 0.001 for both) and higher platelets (p = 0.004 and p < 0.001, respectively) alongside early neutrophils Δ (p = 0.046 and p = 0.033, respectively). Early neutrophils and NLR Δ were independent prognostic factors for both OS (p = 0.014 and p = 0.011, respectively) and PFS (p = 0.023 and p = 0.001, respectively), alongside baseline NLR (p < 0.001 for both) and other known prognostic variables.

Conclusions: Early neutrophils and NLR Δ may represent new dynamic prognostic factors with clinical utility for on-treatment decisions.

Keywords: NLR; dynamics; immunotherapy; inflammatory; prognostic; renal cell carcinoma.

Copyright © 2022 Rebuzzi, Signori, Stellato, Santini, Maruzzo, De Giorgi, Pedrazzoli, Galli, Zucali, Fantinel, Carella, Procopio, Milella, Boccardo, Fratino, Sabbatini, Ricotta, Panni, Massari, Sorarù, Santoni, Cortellini, Prati, Soto Parra, Atzori, Di Napoli, Caffo, Messina, Morelli, Prati, Nolè, Vignani, Cavo, Roviello, Llaja Obispo, Porta, Buti, Fornarini and Banna.